Light is highly adaptive physical energy for performing non-invasive in vivo measurement. However, three problems (see below) specific to a living body occur when performing in vivo optical measurement. The first problem is a scattering phenomenon. Specifically, since light that has undergone scatter transmission or scatter reflection holds propagation historical information and position information to only a small extent, it is very difficult to implement quantitative determination and visualization. The second problem is interference due to intrinsic substances. Spectroscopic measurement is useful for identifying a specific biomolecule. However, intrinsic substances include various fluorescent substances that absorb ultraviolet light and visible light, and may result in an artifact. Therefore, it is difficult to distinguish a signal specific to the target substance. The third problem is a wavelength mismatch. A biomolecule can be specified by vibrational absorption (e.g., C—C, C—H, and C—O). The vibrational absorption wavelength band is the infrared region. A living body has a water content of about 60%. Absorption by water is high in the infrared region, and hinders vibrational spectroscopic measurement on a deep area of tissue. Tissue has high transmittance in a wavelength band of 0.7 to 1.2 micrometers. This wavelength band is referred to as “biological optical window”. As described above, the optical characteristics of the measurement target and the probe wavelength mismatch make it difficult to acquire the biological information when performing in vivo optical measurement.
A contribution of advanced technology to health and medicine in the future can be easily determined based on disease progression and the current technology. A disease develops due to genetic alteration, and progresses through expression of abnormal proteins, a functional change and a structural change in cells and tissue, and development of a subjective symptom. On the other hand, diagnostic technology has been developed to go back through disease progression. Specifically, diagnostic technology has been developed from determination of symptoms based on a doctor's five senses and experience to imaging diagnostic technology that determines a structural change in an early stage.
In recent years, it has become possible to genetically determine the risk of diseases along with significant development of genetic diagnosis technology. However, it is difficult to determine the development timing of a disease. In view of the above situation, it is important to accurately determine the development of a disease in an early stage, and implement less invasive treatment in the future. It is important to determine a functional change that occurs prior to a structural change in order to find a disease in an early stage. Specifically, it is desired to implement molecular imaging of a specific protein in cells and tissue while maintaining the tissue structure that maintains homeostasis.
A molecular imaging method that utilizes light is classified into a probe method that utilizes a fluorescent labeling reagent or the like, and a non-probe method that utilizes the characteristics of an intrinsic substance. Coherent anti-Stokes Raman scattering (CARS) imaging has been known as a non-probe method that solves the above wavelength mismatch (see JP-A-7-294435, for example). However, since the distribution of the measurement target molecules lacks spatial characteristics, the molecular imaging resolution is normally low. Detailed spatial position information about the target molecules is indispensable for clarifying the onset mechanism and the progression mechanism of various diseases. Specifically, it is important to develop molecular imaging based on structural information.
Optical coherence tomography (OCT) has been known as a non-invasive in vivo structural imaging technique. In recent years, in vivo cell imaging that utilizes a broad-band light source using a short-pulse laser beam has been reported. Spectral OCT that extracts spectral information about a sample utilizing the broad-band characteristics of a light source has also been proposed. An OCT signal reflects absorption and scatter due to a sample, and it is possible to extract the spectral information to a certain extent when using a low-scattering sample. However, an error increases when using a scattering body such as tissue, and it is difficult to acquire the spectral information sufficient to identify a substance.